Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer

Author(s): Yen-Shen Lu, MD, PhD1; Eznal Izwadi Bin Mohd Mahidin, MD2; Hamdy Azim, MD3; Yesim Eralp, MD4; Yoon Sim Yap, MD, PhD5; Seock-Ah Im, MD, PhD6; Julie Rihani7; Erhan Gokmen, MD, PhD8; Ahmed El Bastawisy, MD9; Nuri Karadurmus, MD10; Yueh Ni Lim, MD11; Chun Sen Lim, MD12; Le Thanh Duc, MD13; Wei-Pang Chung, MD14; K. Govind Babu, MD15; Konstantin Penkov, MD16; James Bowles, BMedSci17; Teresa Delgar Alfaro, PharmD, MSc17; Jiwen Wu, PhD18; Melissa Gao, MD, PhD17; Khemaies Slimane, MD17; Nagi S. El Saghir, MD19
Source: https://doi.org/10.1200/JCO.24.00144

Dr. Maen Hussein's Thoughts

Myth busted. In aggressive breast cancer, no need to start chemotherapy now, ET and CKD4/6 inhibitors are better tolerated with significant progression-free survival (PFS) benefit and same response rate.

PURPOSE

A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC).

METHODS

In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2– ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator’s choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).

RESULTS

Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator’s judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.

CONCLUSION

First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2– ABC.

Author Affiliations

1National Taiwan University Hospital, Taipei, Taiwan; 2Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 3School of Medicine, Cairo University, Cairo, Egypt; 4Acıbadem Research Institute of Senology, Acıbadem University, Istanbul, Turkey; 5National Cancer Centre Singapore, Singapore; 6Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; 7Independent Patient Advocate, Amman, Jordan; 8Ege University Faculty of Medicine, Izmir, Turkey; 9National Cancer Institute, Cairo University, Giza, Egypt; 10Gülhane Education and Research Hospital, University of Health Sciences, Ankara, Turkey; 11Sarawak General Hospital, Kuching, Sarawak, Malaysia; 12Hospital Sultan Ismail, Johor Bharu, Johor Darul Ta’zim, Malaysia; 13National Cancer Hospital, Hanoi, Vietnam; 14National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 15HCG Curie Centre of Oncology and Kidwai Memorial Institute of Oncology, Bangalore, India; 16Private Medical Institution Euromedservice, St Petersburg, Russian Federation; 17Novartis Pharma AG, Basel, Switzerland; 18Novartis Pharmaceuticals Corporation, East Hanover, NJ; 19American University of Beirut Medical Center, Beirut, Lebanon

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116)

It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.

Read More »

Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study

Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.

Read More »

Final results of RIGHT Choice: Ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2− advanced breast cancer

Nicely done study comparing Ribociclib + ET vs chemotherapy in premenopausal high-risk HR+, HER2-neg patients felt to be high risk. Results showed better efficacy (PFS), tolerability and similar response rates. Of note, >80% of patients had visceral disease or were felt to be rapid progressors. Anti-hormone-based therapy remains king in the HR+ setting.

Read More »

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer

Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.

Read More »